Cushing Syndrome: Clinical Depiction, Causes And Management

Clinical depiction of Cushing Syndrome

Question:

Discuss about the Case Study On Susan Cushing Syndrome.

Cushing syndrome is the clinical depiction as a result of increased levels of plasma glucocorticoids. This condition is rare but most frequently occurs in adults aged 25-50. It may be Adrenocorticotropic hormone (ACTH) reliant or in other instances autonomous. ACTH dependent causes include adrenal tumors that secrete glucocorticoids, diffuse ACTH secreting tumors, micro nodular hyperplasia of the adrenal gland (90% being unilateral) and prolonged exposure to exogenous steroids in the management of autoimmune diseases including Systemic Lupus Erythematosus and rheumatic arthritis. ACTH independent often involve receptor signaling and expression by adrenocortical cells a case seen in Beta adrenergic agonists, ADH, gonadotrophin releasing hormone (GnRH)and in ACTH producing anterior pituitary adenomas (70% of cases). It is also commonly associated with obesity and Diabetes Mellitus Type II and hypertension (National Endocrine and Metabolic Diseases Information Service (NEMDIS), July 2008).

Individuals with Cushing syndrome present with truncal obesity, fatty ‘buffalo’ shoulder, facial obesity hence the “moon face” appearance, poor muscle development, unproportioned arms and legs. Visible purple striae may be seen on the abdomen, arms, thighs and breasts. Women may report of infertility, irregular periods and susceptibility to fractures especially if premenopausal. In some cases, depression and anxiety disorders, hyperglycemia, fatigue and in about 85% hypertension may occur.

The female-male sex based incidence ratio of Cushing syndrome due to adrenal or pituitary tumors is about 5:1.

Extended exposure of body tissues to elevated levels of cortisol(glucocorticoid) causes Cushing syndrome. ACTH-dependent causes are mainly endogenous and include Cushing’s disease (60-70%), CRH-producing hypothalamic tumors and macro nodular hyperplasia. In ACTH-independent cases foundations include ectopic cortisol production by ovarian carcinomas, small cell lung carcinomas and neuroendocrine tumors resulting in high ACTH levels. Overproduction of endogenous glucocorticoids independent of ACTH is on most occasions due to adrenocortical neoplasms(adenomas). In a homeostatic body system, the hypothalamus secretes Corticotrophin releasing hormone(CRH) to the anterior pituitary which releases Adrenocorticotrophic Hormone that act on the Zona fasciculata producing cortisol from the progenitor cholesterol. The plasma reference levels are 140-700nmol/L in the morning and 80-350nmol/L at midnight (Biochemistry Reference Ranges Goodhope,2012). Cortisol functions to stimulate gluconeogenesis in fasting state, downregulates the production of interleukin-12and Tumor Necrosis Factor Alpha by antigen presenting cells upregulating the production of IL-4, IL-10 and IL-13 by the T helper cells resulting in prevention of an overactive immune response.

Furthermore, cortisol antagonizes the functioning of insulin. This results insulin resistance and decreased energy dependent translocation of glucose by the GLUT-4 transporter this in the case of Cushing syndrome the hyperactivity of cortisol results in the manifestation of diabetes mellitus type II. In calcium homeostasis in bone, cortisol results in increased resorption, there is also increased potassium efflux and reduced intestinal calcium absorption. Excess of cortisol causes osteoporosis and hyperkalemia in this case (The Journal of Clinical Endocrinology and Metabolism. 15 (2): 176–81).

Causes of Cushing Syndrome

Cortisol also functions to increase the level of free amino acids through protein catabolism. It also inhibits immunoglobulins IgA and IgM, in hypercortisolism, there is evident hyperlipidemia and decreased peripheral glucose utilization as a result of liberated amino acids. There is also evident muscular atrophy, thin skin and subcutaneous tissues, scraggy thin hair and uneven fat distribution. Significant diuretic effects of cortisol occur in high cortisol levels in serum, the potassium ions are excreted and sodium retained. The salt and water retention results in the round moon face appearance seen in Cushing Syndrome

The role cortisol in the CNS cannot be overlooked. In cognition it is involved the hippocampal formation on short term memory. The control of the circadian rhythm (McDonald’s veterinary endocrinology and reproduction (5th ed) via control of the suprarchiasmatic nucleus. In Cushing syndrome sleep and mood disorders are common. Depression may also occur and psychologic stress exaggerated. In obese individuals there is elevated cortisol courtesy of cortisol regeneration from cortisone by hydroxysteroid 11-beta dehydrogenase 1.

Susan’s respiratory rate was 30 breaths per minute which is higher than the normal range of 12-20 breaths per minute, she is also hypertensive with a recorded blood pressure of 160/90 mmHg (normal range of 90/60- 120/80 mmHg). Her body temperature was at 35.0°C, this is below the normal reference range of 36.5°C-37.3°C. There is also a reported increase in the pulse, the recorded value is 128bpm, the value is elevated off the normal range of 60-100bpm. There is subclinical pain with a score of 0/10. The urinary output is reduced to 5mls per hour (normal 30-80ml/per hour).

The respiratory recovery after anesthesia is slow and there is a reflex apnea due to the compensatory mechanisms of the surgically induced hypoxia. The recovery from the respiratory depression takes elimination of carbon dioxide and reduction in the ventilation to perfusion ratios in the lungs. The post-op hypertensive state was triggered by the reflex reaction to glucocorticoid suppression. There is also marked reduction of the production of aldosterone. This mechanisms involve a secondary adrenal insufficiency resulting from the suppression of the Hypothalamic-pituitary adrenal axis (HPA). Suppression of the renin angiotensin system and reduction of the diuretic mechanism of action of cortisol produce a resultant increase in the cardiac output thus an elevated blood pressure.

Additionally, the basal body temperature is reduced, this is as a result of the suppression of the pontine temperature control centers and the recovery phase from the surgical anesthesia. Susan is also in a steroid crisis and the physiological mechanisms are sabotaged by the sudden withdrawal of he obviously high levels of cortisol. The reduction is the metabolism by these two individual triggers result in the transient hypothermia. Coupled with the hypothermic state is the increased pulse rate. This is produced as a result of tachycardia and increased nervous stimulation after the surgical pressure. The body registers a shock which culminates in the increase in the heart rate. Reduction in aldosterone and altered feedback to the HPA axis causes a reduced production of urine. There is recorded retention of sodium of potassium ions thus a hypovolemic shock. A conglomeration of all these pathological cases result in Susan’s post-operative presentation.

ACTH-dependent causes

Considering the presentation, Susan’s management involve the monitoring of all her vital signs. The values are measured and recorded two hourly. Any notable change is reported for further intervention. Electrolyte values are also taken on a frequent schedule especially in the first 48 hours after the surgery. Administer intravenous fluids and account for the fluid intake and output at regular intervals. Pain is also monitored and analgesics administered accordingly to alleviate pain. To avert any episode of hypovolemic shock or Addisonian crisis, Cortisol is administered to replace the inadequate hormonal levels. Care for the laparoscopic site, the wound is drained and cleaned using a sterile technique to reduce the risk of an infection. The indwelling urinary catheter is removed on the first day post-op and a clear liquid diet is started on the first day. Dietary progression is made on a need-basis. Psychosocial support is given to relieve anxiety.

On discharge, the Susan and any appropriate family members will get an explanation and schedule on the take home medication and prescription. General health messages on the effect of the surgical procedure and physiological response to the resultant procedure. The messages include dietary management of sugar, side effects of glucocorticoid therapy and the importance of physical exercise of the overall outcome of the recovery process. Details of the next checkup are also provided for .Susan also has to report any alarming signs in the process.

Susan’s condition requires an entire team approach to effectively manage her condition. Apart from her the primary medical and nursing team the social worker, nutritionist and the health educator are involved. The integration of the entire team is required to produce an outcome sufficient to make Susan’s life more productive and fruitful. The medical condition will become more lucid.

The social worker provides is the backbone of the familial responsibility at hand. The care of all her three children verses her income from the casual employment. She does require an extensive monetary plan and linking up to more agencies to provide financial support and education to children. On the returns from her wages, the social worker provides liaises with monetary organizations that provide saving plans and insurance policies suitable to the financial muscle Susan has.

The nutritionist evaluates and provides the nutritional needs of Susan. They assist in providing a treatment plan which may include special diets, foods that help ease swallowing, dietary changes as a result of the condition and also patient and family education on nutrition topics related to Susan’s condition.

ACTH-independent causes

The health educator will also be of much importance in educating Susan and his family on topics related Cushing’s syndrome and other general health concerns. This include causes, prevention and even treatment. Topics concerning usage of over the counter drugs can also be handled by the health educator. Others include personal hygiene and general cleanliness.

Conclusion

Susan is obese and presents with a typical case of Cushing syndrome, determination of her differential diagnosis is based on her presenting case of primary depression and alcoholism. The diagnostic approach to the cause of the hypercortisolism involves a 24-hr urine sample collection and assay of cortisol levels. In elevated cortisol levels, a low dose of dexamethasone (2mg/day for 2 days) is administered and on the subsequent urine collection if the cortisol is suppressed by more than 50% then it is definitive case (European Journal of Endocrinology, vol. 176, no. 5, pp. 613–624, 2017). When suppression is non-evident a repeat test is done with a higher dose of 8mg /day for 2 days and as in the case there would be no suppression because the cause of ACTH suppression secondary to an adrenal tumor. The adrenal tumor is visualized via a CT Scan and as indicated a surgical plan of a right adrenalectomy is done. The procedure is done and she has due rehabilitation and integration to her state.

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